tbuckley/cabot-search huggingface dataset:
Factors associated with duration of care in community direct-to-patient (DTP) pharmacies among Chinese cancer patients taking PD-1/PD-L1 inhibitors: Results from a real-world study.
Authors: Sheng Han, Yi Wen, Xin Zheng, Ning Ruo Wang, Jin Hua, He Zhu
Journal: Journal of Clinical Oncology (2022)

e18654 Background: Several PD-1/PD-L1 inhibitors have been approved in China for multiple cancers. Community DTP pharmacies play an important role in both drug distribution and patient management. Using real-world patient management data, we explored the factors associated with duration of care in community DTP pharmacies among cancer patients using PD-1/PD-L1 in the country. Methods: This is a retrospective cohort study using real-world sales and follow-up data routinely collected from 79 Medbanks community DTP pharmacies between Jan 1, 2019 and Mar 31, 2021. Duration of follow-up (DoFU) was defined as the time interval between first PD-1/PD-L1 purchase and last follow-up contact. Duration of drug purchase (DoDP) was defined as the time interval between the first and the last PD-1/PD-L1 purchase date plus a buffer period which was determined based on the amount of last purchase. Covariates included: gender, age, enrollment in a patient access program (PAP), experience of adverse events (AE) during treatment, patient’s awareness of the disease, and follow-up response rate (FRR; &lt; 30%, 30-70%, &gt; 70%). Uni- and multivariate Cox regression models were conducted to assess the association of DoFU/DoDP with predicting variables among both total population and cancer specific sub-populations. Results: A total of 23,559 patients were evaluated (median age: 61 yrs; male: 73%). The three most common cancer types were lung cancer (51.90%), hepatobiliary cancer (19.69%) and esophageal cancer (9.98%). The median DoFU and DoDP were 6.3 month (95% CI: 6.23̃6.50) and 2.3 months (95% CI: 2.27̃2.33). In multivariate Cox regression model, factors associated with longer DoFU included enrollment in PAP (HR = 0.52, p &lt; 0.001), experience of AE during treatment (HR = 0.71, p &lt; 0.001), FRR 30-70% (HR = 0.66, p &lt; 0.001; ref: &lt; 30%) and FRR &gt; 70% (HR = 0.56, p &lt; 0.001; ref: &lt; 30%); factors associated with longer DoDP included enrollment in PAP (HR = 0.90, p &lt; 0.001), experience of AE during treatment (HR = 0.84, p &lt; 0.001) and FRR &gt; 70% (HR = 0.80, p &lt; 0.001; ref: &lt; 30%). The protective effects of PAP, AE and higher FRR on DoFU and DoDP were also observed in the three main cancer specific sub-populations. Conclusions: High quality patient management service provided in community DTP pharmacies is significantly associated with longer duration of care, which implies the important role of DTP pharmacies in the longitudinal care of cancer patients. A comprehensive service package should be developed and applied in community DTP pharmacies for cancer patients in order to better address their medical needs and financial strain.
Safety of dual checkpoint-blockade with PSB205, an anti-PD-1/CTLA4 monoclonal antibody combination, manufactured and dispensed as a single product: A phase 1 study.
Authors: Rashmi Chugh, Judy S. Wang, Anthony J. Olszanski, Breelyn A. Wilky, Paul Algate, Leah Plato, Alexander I. Spira, Borys Korchin, Jelle W. Kylstra
Journal: Journal of Clinical Oncology (2022)

2611 Background: PSB205 is a new biological agent consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1) expressed in a fixed ratio (2:1) from a single cell-line, manufactured as one product and dispensed from a single vial. PSB205 was designed to optimally balance efficacy and safety through differential target coverage of PD-1 and CTLA-4: the anti-CTLA-4 antibody was engineered to have a shorter half-life to modulate exposure and lower risk of immune-related adverse events (irAEs). Methods: We report safety data from a first-in-human study, conducted in standard 3+3 Phase 1 dose escalation format, enrolling subjects with refractory solid tumors with mixed histologies, who had exhausted available standard treatments. Primary objectives were safety (including Dose Limiting Toxicities), tolerability and selection of a Phase 2 dose. Secondary objectives were PK and preliminary evaluation of effectiveness. Treatment was Q3 wks. Inclusive the 1st week following the 2nd infusion, the DLT-period was 28 days. Results:Nine US-centers enrolled 27 subjects, representing 19 tumor histologies, in 5 ascending dose cohorts ranging from 0.1 mg/kg to 5 mg/kg; an additional N = 49 pts were dosed in expansion cohorts at 5 mg/kg and 400 mg (fixed dose). Median number of prior systemic treatments for metastatic disease was 4. No DLT was observed at any of dose level evaluated. The most frequent Treatment-Related Adverse Events (TRAE) reported were diarrhea (9%), Infusion-Related Reaction (IRR) (5%) and fatigue (4%). Among the subset (N = 33) who completed at least 4 cycles of treatment, the most common TRAE were diarrhea (21%), IRR (12%), Fatigue (9%), and irAEs, specifically colitis, rash and arthralgia (6% each symptom). Most TRAEs were Grade 1 /2, with just 1 case each of diarrhea and colitis Graded as G 3/4. Tumor responses (all PRs) were observed at dose levels of 3 mg/kg and 5 mg/kg in 4 pts - 1 each with with RCC, SCLC, HNSCC and gastric cancer. Conclusions: PSB205 provides dual checkpoint blockade with a very tolerable side effect profile, with less AEs than typically noted in published studies of anti-PD1 and anti-CTLA-4 combination therapy. Further studies are ongoing to confirm this observation. Dose levels of 5 mg/kg and 400 mg fixed were selected for Phase 2, which has commenced enrollment. Clinical trial information: NCT03986606.
Quantifying the absolute benefit of neoadjuvant chemotherapy followed by definitive therapy in patients with muscle-invasive bladder cancer: A systematic review and meta-analysis.
Authors: Waleed Ikram, Syed Arsalan Ahmed Naqvi, Ammad Raina, Ezza Fatima, Rabbia Siddiqi, Mahnoor Islam, Noureen Asghar, Kaneez Zahra Rubab Khakwani, Ahsan Masood Khan, Syed A. Hussain, Alan Haruo Bryce, Irbaz Bin Riaz, Parminder Singh
Journal: Journal of Clinical Oncology (2022)

4594 Background: Cisplatin based neoadjuvant chemotherapy (NAC) followed by definitive therapy improves survival in patients with muscle invasive bladder cancer (MIBC). However, the clinical benefit of NAC might vary with the choice of definitive therapy. Therefore, we assessed the absolute benefit of NAC followed by radical cystectomy or radical radiotherapy separately using the totality of evidence. Methods: MEDLINE and EMBASE were systematically searched to identify randomized trials assessing cisplatin based neoadjuvant chemotherapy followed by either radical cystectomy or definitive radiotherapy in patients with MIBC. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). Treatment effects were expressed as hazard ratios (HR) with 95% confidence interval (CI). Incidence rate ratios were calculated to estimate time to event outcomes for trials not reporting HR. A random-effects DerSimonian-Laird meta-analysis was conducted. Absolute effects were then obtained using baseline risks from the control arm of RCTs. Results: Of 4887 studies identified, 13 trials with 2529 patients were included in this meta-analysis. Most trials included patients with T2-4 and N0 patients and only 3 trials included patients with node positive disease. Total of 180 (47%) DFS events were observed with NAC+RC compared to 213 (56%) events in RC alone (HR: 0.72; 95% CI: 0.59-0.89) and 346 (58%) OS events were observed with NAC+ RC compared to 385 (52%) events in RC alone (HR: 0.80; 95% CI: 0.69-0.92). Total of 186 (70%) DFS events were observed with NAC + radiotherapy compared to 205 (71%) events in radiotherapy alone (HR: 0.91; 95% CI: 0.74-1.12) and 263 (58%) OS events were observed with NAC+ radiotherapy compared to 294 (61%) events in radiotherapy alone (HR:0.93; 95% CI: 0.79-1.08). Conclusions: The choice of definitive therapy after cisplatin-based NAC impacts survival in patients with MIBC. RC after NAC improved DFS (114 fewer events per 1000 events) and OS (76 fewer per 1000 events) whereas radiotherapy after NAC showed no survival benefit. [Table: see text]
Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM).
Authors: Santiago Ponce, Susana Cedres Perez, Charles Ricordel, Nicolas Isambert, Victor Levitsky, Thomas Birkballe Hansen, Magnus Erik Jaderberg, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2022)

8561 Background: MPM is an aggressive malignancy without curative treatment. ONCOS-102 is an oncolytic adenovirus expressing GM-CSF (Ad5/3-D24-GMCSF) with a clinically documented ability to stimulate local and systemic immune responses and re-modulate the tumor microenvironment, both as a monotherapy and in combination with anti-PD1 blockade. The study objectives included determining safety and tolerability, efficacy and immunological activation in repeat tumor biopsies, and correlations with clinical outcomes. Methods: Following a safety run-in of n = 6 pts, 25 patients were randomized to receive ONCOS-102 intratumorally under CT or US guidance at a dose of 3 x 10 11 Virus Particles on Day 1, 4, 8, 36, 78 and 120, plus six cycles of P/C starting on Day 22, or control comprising six cycles of P/C only. Both treatment-naïve (1L) and previously treated patients (2L) were enrolled. Imaging was done at baseline, Day 43-64 and 127-148 and tumor biopsy were collected at baseline and at Day 36. Final survival analysis (n = 25) was performed after 30 mo follow up. Multiplex immunofluorescence for immune cell subsets, RNASeq and qPCR was performed on repeat tumor samples. Results: The most frequent adverse events were anaemia, neutropenia and asthenia reported by &gt; 50% in both groups with more frequent reports of pyrexia and nausea in the experimental (exp) group. No difference in the rate of severe events (Gr 3/4 acc to NCI CTCAE vs 4.0) were observed. 30-month survival rate (n = 25) was 34.3 % vs 18.2 % (NS) with mOS of 19.3 mo (95% CI: 4.6, NA) vs 18.3 mo (95% CI: 3.1, 28.9) in the exp group vs control. For patients treated in the 1L setting, 30 mo survival was 33.3 % in the exp group (n = 8) and 0% in the control group (n = 6) with mOS of 25.0 months and 13.5 months, respectively (NS). mPFS was unchanged from prior cut-offs; 9.8 months in the exp group and 7.6 in the control (NS). ONCOS-102 + P/C induced a pronounced increase in tumor infiltration by CD4+, CD8+ and granzyme B expressing CD8+ T-cells as well as M1:M2 macrophage polarization in patients with disease control (n = 13) vs progressing patients (n = 3). The data from RNAseq and qPCR analysis will be presented. Conclusions: The addition of ONCOS-102 to P/C was well tolerated by MPM patients and resulted in numerically improved 30-month survival rate in the overall population, and improved mOS in chemotherapy-naïve patients, albeit not statistically significant. Substantial immunological activation in tumor associated with ONCOS-102 was demonstrated, correlating with clinical benefit. Further exploration of ONCOS-102 as a treatment option in MPM is warranted Clinical trial information: NCT02879669.
Multiomics analysis of pediatric solid tumors within the INFORM precision oncology study: From functional drug profiling to biomarker identification.
Authors: Dina ElHarouni, Heike Peterziel, Kathrin Schramm, Till Milde, Sina Oppermann, Ina Oehme, Olaf Witt, Matthias Schlesner, Natalie Jäger
Journal: Journal of Clinical Oncology (2022)

10036 Background: Within the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) registry over 1200 childhood malignancies were molecularly profiled using next generation sequencing to identify therapeutic targets. Nevertheless, high evidence targets were only detected in 5% of cases and only 50% of the patients were identified with druggable pathways, while the remaining cases lacked druggable alterations. Thus, an ex-vivo functional drug response profiling platform for pediatric solid tumors has been established within the INFORM program to identify novel biomarkers and unravel molecular mechanisms associated with drug response profiles for clinical translation. Methods: Solid tumors from 97 paediatric patients were screened against a library of 76 drugs. A quality control classification decision tree was designed to select the samples for further analysis. Whole exome sequencing, low-coverage whole genome sequencing, and RNA-seq were used to analyze the molecular profiles of the samples. Molecular features were filtered to retain oncogenic and druggable events. Five data feature views (mutations, mRNA, gene fusions, CNVs, and drug responses) were used to train a Multi-Omics Factor Analysis (MOFA) model to identify prominent latent factors. Results: 81 samples passed the quality control inclusion criteria of which 76 samples had available omics data profiles. Quantitative drug profiling measurements were reported using the selective asymmetric drug sensitivity score.The multi-omics analysis captured five entity-specific omics signatures of Ewing sarcoma, Wilms tumor, BCOR sarcoma, neuroblastoma and ependymoma. Moreover, the analysis revealed sensitivity to navitoclax in neuroblastoma samples with PHOX2B-GATA3 overexpression, and an association between MEK inhibitor sensitivity and an expression signature in Wilms tumors. Conclusions: The combination of functional drug and multi-omics profiling enabled the identification of novel biomarkers for drug sensitivities in pediatric solid tumors. As we continue to expand the number of patient samples evaluated with our drug sensitivity platform, this dataset will provide insights for novel drug targets, and could unravel key molecular events and mechanisms acting towards personalized therapies.
Bone biomarkers and overall survival (OS) in men with advanced hormone-sensitive prostate cancer (HSPC): Results from SWOG S1216, a phase III trial of ADT +/- orteronel.
Authors: Primo "Lucky" N. Lara, Edward Mayerson, Erik Gertz, Catherine Tangen, Amir Goldkorn, Marta Van Loan, Maha H. A. Hussain, Shilpa Gupta, Jingsong Zhang, Mamta Parikh, Przemyslaw Twardowski, David I. Quinn, Nicholas J. Vogelzang, Ian M Thompson, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2022)

5071 Background: Circulating bone biomarkers (BB) are strongly prognostic for OS in castration-resistant PC (CRPC). We prospectively evaluated BB in men with HSPC in S1216, a trial that established new OS benchmarks. We sought to identify patient (pt) subsets with differential OS outcomes as defined by BB. Methods: Markers of bone resorption [CTx;PYD] &amp; formation [CICP;BAP] were assessed. Pts were randomly divided into training (1/3) &amp; validation (2/3) sets. In the training set, recursive partitioning of OS was used to identify the ideal dichotomous cutpoint for each BB &amp; for a combination of biomarker split points to define prognostic groups. In the validation set, Cox PH models were used to assess impact of BB on OS, adjusted for pt &amp; tumor characteristics. Adjusted odds ratios for 3-year OS based on BB &amp; baseline clinical factors were developed using logistic regression to estimate receiver operating characteristic (ROC) curves. Results: Of 1,279 men, 949 had baseline BB. Median age–68y; median PSA-28 ng/dL; Gleason&gt;7: 60%; Zubrod PS 0/1-97%. Values of BB at the median &amp; at cutpoints maximized for OS were identified. For 3 of the BB, the cutpoint was at the ̃85 th %ile; for PYD it was at the median. Recursive partitioning algorithms applied to the training set identified 4 groups with differential OS based on a dichotomous split of CTx in combination with additional CICP splits within each group. Hazard ratios (HR) for OS based on elevated BBs are shown. ROC analysis showed that only BAP &amp; PYD had significantly higher AUC(0.73;0.74) compared to AUC of baseline clinical factors(0.71) w/ p=0.02 and 0.03 respectively. There was no evidence of BB x treatment interaction (all p&gt;=0.2). Conclusions: In men initiating ADT for HSPC, elevated BB are strongly prognostic for worse OS. BB levels alone &amp; in combination with pt/tumor characteristics identify unique subsets of men with high probability of being alive at 3 years from ADT initiation. These results validate the clinical value of BB in the HSPC state, extending BB utility beyond CRPC. Clinical trial information: NCT01809691. [Table: see text]
A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma (CERPASS).
Authors: Andrew Mark Haydon, Nikhil I. Khushalani, Caroline Robert, Daniel Brungs, Frances A. Collichio, A. Dimitrios Colevas, Annette May Ling Lim, Ragini Reiney Kudchadkar, Wanxing Chai-Ho, Gregory A. Daniels, Jose Lutzky, Jenny HJ Lee, Ann W. Silk, Celeste Lebbe, Jean-Jacques Grob, Margaret Smith, Matthew G. Fury, Muhammad Alamgeer, Andrew Graham Hill, Michael Robert Migden
Journal: Journal of Clinical Oncology (2022)

TPS9593 Background: RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity, which is further improved by combining anti-PD-1 therapy. The prognosis for advanced and metastatic cutaneous squamous cell carcinoma (CSCC) remains poor for many patients despite the adoption of cemiplimab and pembrolizumab as a standard treatment. Preliminary results from IGNYTE, a phase I/II clinical study of RP1 in combination with nivolumab showed a high rate of deep and durable responses in patients (pts) with CSCC. This study is evaluating the efficacy and safety of cemiplimab ± RP1 versus cemiplimab alone in advanced CSCC. Methods: This global, multicenter, randomized phase 2 study is enrolling pts with metastatic or unresectable, locally advanced CSCC who are not candidates for/refuse surgery and/or radiation therapy. Key eligibility criteria include no prior treatment with anti-PD1/PD-L1 antibodies or oncolytic viruses. The clinical trial is enrolling approximately 180 pts from centers in the EU, Australia, Canada, and USA. Pts are randomized in a 2:1 ratio to receive combination therapy or monotherapy respectively. Pts receive 350 mg of cemiplimab intravenously (IV) Q3W for up to 108 weeks. In the RP1 + cemiplimab arm, RP1 is injected intratumorally at a starting RP1 dose of 1 × 10 6 plaque-forming units (PFU)/mL alone, followed by up to 7 doses of RP1 at 1 × 10 7 PFU/mL Q3W together with the same dose of cemiplimab. Pts in the combination arm may receive up to 8 additional RP1 doses if protocol specific criteria are met. No crossover is allowed. Pts are stratified by disease status (nodal or distant metastatic or locally advanced CSCC) and prior systemic therapy. Tumor assessments are performed every 9 weeks. The dual independent primary endpoints are overall response rate and complete response rate, both by a blinded independent review. Secondary endpoints include safety, progression-free survival, duration of response, and overall survival. Exploratory endpoints include quality of life, and immune biomarker analyses. This trial is currently enrolling pts. Clinical trial information: NCT04050436.
Randomized trial of atorvastatin during and following receipt of doxorubicin for breast cancer and lymphoma (WF-98213).
Authors: William Gregory Hundley, Ralph D'Agostino, Teresa Crotts, Mary Helen Hackney, Jennifer Jordan, Bonnie Ky, Lynne I. Wagner, David Herrington, Joseph Yeboah, Kerryn Reding, Amy Ladd, Steve Rapp, Sandra Russo, Nathaniel S. O'Connell, Kathryn E. Weaver, Emily Van Meter Dressler, Yaorong Ge, Susan Anitra Melin, Vinay K. Gudena, Glenn Jay Lesser
Journal: Journal of Clinical Oncology (2022)

12072 Background: Statins taken for cardiovascular (CV) indications by breast cancer (BC) and lymphoma survivors during doxorubicin (DOX) treatment may attenuate left ventricular ejection fraction (LVEF) decline, but statin impact among these survivors with no CV indications is unknown. Methods: In 279 patients from 31 cancer centers, we conducted a double blind, placebo-controlled, 24-month randomized trial of 40mg/day atorvastatin among those receiving DOX for BC or lymphoma. At pretreatment, six and 24 months after initiating DOX for BC or lymphoma, we assessed LV volumes, strain, mass, and LVEF (via cardiac magnetic resonance), cognitive function and serum markers of inflammation. Using a linear model adjusted for pretreatment measures, our primary analysis assessed change in LVEF over time by randomization group. Results: Participants were aged 49±12 years; 92% women, 83% white race. The mean pooled LVEF decline from pretreatment to 24 months was 62.2±6.0% to 57.6±6.3% (p &lt; 0.001). Adjusting for pretreatment LVEF, 24-month declines in LVEF averaged 3.5±0.5% and 3.3±0.5% respectively for placebo vs statins (p = 0.83). Both randomized groups were similar for: incidence of &gt; 10% change in LVEF, LV strain, LV mass, cognition and inflammation biomarkers, including among those &gt; 90% study drug compliant (p &gt; 0.05 for all). Conclusions: In BC and lymphoma survivors with no existing indication for statin therapy, prospective statin administration does not appear to impact LVEF declines two years after doxorubicin. Clinical trial information: NCT01988571. [Table: see text]
Efficacy of anlotinib for advanced SCLC patients: A real-world study.
Authors: Yu Yao, Xiaopeng He, Xinli Hou, Hehe Liao
Journal: Journal of Clinical Oncology (2022)

e20621 Background: Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor, which has been approved as a third-line therapy for patients with advanced small cell lung cancer (SCLC) by NMPA in Aug 2019. ALTER 1202 trial has demonstrated that anlotinib significantly prolonged progress-free survival (PFS) and improved disease control rate (DCR) of advanced SCLC patients. Since the efficacy of patients in real clinical practice is affected by many factors, the objective of this study was to assess the efficacy of anlotinib for patients with advanced SCLC in real world. Methods: This is a multi-center, non-interventional, prospective real-world study and all registered data are collected from real clinical practice cases. Patients diagnosed as advanced SCLC and treated with anlotinib were included. The primary endpoint was PFS, and secondary endpoints included overall survival (OS), objective response rate (ORR), DCR and safety. Results: Until Dec 2021, a total of 44 eligible patients were included, with a median age of 62 years, including 34 males (77.3%) and 10 females (22.7%). Among them, 38 patients (86.4%) were diagnosed as a limited stage SCLC and 6 patients (13.6%) diagnosed extensive stage. All patients have not received other targeted therapies before. The median PFS was 6.0 months (95%CI 2.4-5.8), and the median OS was 15.9 months (95%CI 9.1-18.83). At the data cut-off date, 1 patient was assessed as CR, 22 patients were assessed as PR, 15 patients were assessed as SD and 4 patients were assessed as PD. The ORR was 52.3% and the DCR was 86.4%. Conclusions: Significant improvement in OS and PFS were found for advanced SCLC patients in this real-world study. This exhibited that anlotinib has a potential efficacy over previous treatment models. Of course, safety must be further observed subsequently.